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The interaction of p53 and MDM2 genes in cancers, in silico studies and phylogenetic analysis

Author(s): A. Jayaraman

Journal: Biology and Medicine
ISSN 0974-8369

Volume: 3;
Issue: 3;
Start page: 1;
Date: 2011;
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Keywords: p53 | MDM2 | genes | cancer | in silico studies | phylogeny | cell cycle regulation

The normal cell cycle process is a crucial process and is generally mediated by a number of regulatory genes. One ofthe most important regulators is the tumor suppressor p53, which in turn is regulated by MDM2 gene. The expressionof p53 and MDM2 is found to be frequently altered in many cancers and metastasis/ relapses .This is the first reportto look at the evolutionary history of these genes to decipher the role of these genes in the tumorigenesis processusing in silico methods. We also found that they showed high degree of sequence similarity across the mammalianspecies, indicating that these species probably share parallel cancer causing mechanisms. Their individual unrootedphylogenetic tree formed 5 clusters each; however, p53 gene was found in a large number of species whereasMDM2 was found in smaller number of species. The role of MDM2 is therefore limited and occurs in fewer speciesacross the mammalian species. It is evident that these molecules play an important role in the cancer process,perhaps responsible for relapses and hence need to be explored further as therapeutic targets. Such studies that arebased on evidence from paleontology and genetics suggest that mechanisms of cancer are embedded deeplythroughout evolution. Understanding the phylogenetic evolution of these genes could help in furthering our knowledgeon the mechanisms involved in cancer.
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